Although significant progress has been made in describing a variety of secretory cell systems and some information is currently available regarding secretory dysfunction in disease, the molecular and cellular events directly involved in salivary gland acinar cell differentiation, tissue specific gene expression, cell growth and the actual molecular events that occur in the dysfunction of these cells during disease still constitutes a poorly understood area of cell biology. The development of salivary gland acinar cell lines with moderate to high level of cytodifferentiation and normal secretory function would greatly facilitate these types of studies. Over the last several years, we have helped to define the nutritional, hormonal and growth requirements for the primary culture of rat submandibular and parotid acinar cells, as well as identifying the important extracellular matrix proteins necessary for maintaining cytodifferentiation and secretory function while in culture. We are proposing to utilize this information along with a variety of plasmids containing various transforming agents, to begin to develop moderate to highly differentiated rat parotid and submandibular acinar cell lines. We plan to establish "immortalized" cell lines via transfection. The resultant cell lines will be characterized after transfection, low passage, during crisis and immortalization. Morphological, physiological and biochemical procedures will be performed to select for, and to fully characterize, those cell lines that meet the appropriate level of different tion.